Influenza is characterized by recurrent annual epidemics and periodic major worldwide pandemics. Because of the high disease-related morbidity and mortality, direct and indirect socio-economic impacts of influenza are enormous. In the last 100 years, there have been 3 major influenza pandemics. It has been about thirty years since the last pandemic. A new pandemic is considered imminent and one of the biggest challenges facing public health systems today. With recent technical progress, it has also become possible for bio-terrorists to create potential pandemic viral strains faster than natural evolution of the viruses. Therefore, a broad-spectrum therapeutic/prophylactic product for influenza is critically needed. We have identified a drug lead, Fludase(tm), which targets on all strains and subtypes of influenza including the potential pandemic strains. With the funding from a Phase I Biodefense SBIR application, we have demonstrated its efficacy against a variety of influenza viruses. Unlike the currently available Flu vaccines, Fludase(tm) does not need to be updated yearly. Fludase(tm) can be produced cost effectively and can be readily available at the onset of a natural pandemic or bio-warfare, and for annual epidemics. As a protein-based therapeutic agent administered topically and locally, Fludase(tm) can also potentially avoid the side effects and the risk of generating drug resistant viruses associated with the currently available expensive antiviral compounds. The objective of this grant application is to complete all necessary pre-clinical development and to initiate early stage clinical development of Fludase(tm).